Abstract Alzheimer?s disease (AD) is a degenerative disease of the brain associated with aging which is responsible for profound morbidity and mortality. Ninety-nine percent of cases are of unknown cause, and not created by an abnormal gene. The disease progressively affects memory, judgment, abstraction, perception, visual-spatial abilities and language as well as other functions. There is also sterile inflammation of brain associated with the progression of AD. The microbiota is being extensively studied and has been found to be critically important for health and disease. The role of the microbiota in AD is suggested by the early onset of olfactory dysfunction in the disease as well as many other studies that document changes in microbiota associated with ageing and AD progression. Such microbiota changes are also observed in mouse models, yet no clear candidate microbes for promoting or delaying AD have been identified. We have established a Functional Microbiomics Core (FMC) at UofL that supports the work of many faculty by providing germ-free, gnotobiotic mice as well as anaerobic culturing and characterization of microbiota signatures by 16S sequencing. In this administrative supplement, we propose to expand the FMC to include AD mouse models. We will rederive the well-established AD models APP/PS1 and 3XTg-AD and maintain these as germ-free and test them in behavioral models. We will examine the role of bacterial amyloids in seeding the brain AB by using the E.Coli strains expressing the amyloid protein curli. In Aim2, we will recolonize the germ-free APP/PS1 mice with AD or control stool samples to generate stable humanized microbiota mice that will serve as models for examining the promoting and protective roles of specific microbiota populations in AD. This work has important implications for all neurological conditions involving misfolded proteins and microbiota. The approaches outlined here will be highly productive and rewarding both interms of understanding disease mechanisms and developing novel preventive/therapeutic strategies.